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R Clement

Publications and source records attributed to R Clement.

At least 19 recordsLinked to original sources
PubMed2001

Pharmacokinetic and safety profile of desloratadine and fexofenadine when coadministered with azithromycin: a randomized, placebo-controlled, parallel-group study.

BACKGROUND: Significant cardiac toxicity has been associated with some older antihistamines (eg, terfenadine and astemizole) when their plasma concentrations are increased. There is thus a need for a thorough assessment of the cardiac safety of newer antihistamine compounds. OBJECTIVE: This study was undertaken to assess the effects of coadministration of desloratadine or fexofenadine with azithromycin on pharmacokinetic parameters, tolerability, and electrocardiographic (ECG) findings. METHODS: Healthy volunteers aged 19 to 46 years participated in this randomized, placebo-controlled, parallel-group, third-party-blind, multiple-dose study. Subjects received desloratadine 5 mg once daily, fexofenadine 60 mg twice daily, or placebo for 7 days. An azithromycin loading dose (500 mg) followed by azithromycin 250 mg once daily for 4 days was administered concomitantly starting on day 3. Group 1 received desloratadine and azithromycin, group 2 received desloratadine and placebo, group 3 received placebo and azithromycin, group 4 received fexofenadine and azithromycin, and group 5 received fexofenadine and placebo. RESULTS: The results of the pharmacokinetic analysis revealed little change in mean maximum concentration (Cmax) and area under the concentration-time curve (AUC) values for desloratadine with concomitant administration of azithromycin: Cmax ratio, 115% (90% CI, 92-144); AUC, ratio 105% (90% CI, 82-134). The corresponding ratios for 3-hydroxydesloratadine were 115% (90% CI, 98-136) and 104% (90% CI, 88-122), respectively. A substantial increase was observed in mean Cmax and AUC values for fexofenadine when administered with azithromycin: Cmax, ratio, 169% (90% CI, 120-237); AUC ratio, 167% (90% CI, 122-229). Compared with the group receiving desloratadine and azithromycin, subjects receiving fexofenadine and azithromycin also displayed greater variability in pharmacokinetic parameters for the antihistamine. Mean Cmax and AUC values of azithromycin were slightly higher when administered with desloratadine (Cmax ratio, 131% [90% CI, 92-187]; AUC ratio, 112% [90% CI, 83-153]) but were lower when given in combination with fexofenadine (Cmax ratio, 87% [90% CI, 61-124]; AUC ratio, 88% [90% CI, 65-1201). The most common adverse event for all regimens was headache, reported in 20 (22%) subjects. All combinations of desloratadine or fexofenadine with and without azithromycin were well tolerated, and no statistically significant changes in PR, QT, or QT, interval, QRS complex, or ventricular rate were observed. CONCLUSIONS: Small increases (<15%) in mean pharmacokinetics of desloratadine were observed with coadministration of azithromycin. By contrast, peak fexofenadine concentrations were increased by 69% and the AUC was increased by 67% in the presence of the azalide antibiotic. Based on the reported adverse-events profile and the absence of changes in ECG parameters, the combination of desloratadine and azithromycin was well tolerated. This study suggests that desloratadine has a more favorable drug-interaction potential than does fexofenadine.

Adolescent↗
PubMed2000

Respiration as the main determinant of carbon balance in European forests.

Carbon exchange between the terrestrial biosphere and the atmosphere is one of the key processes that need to be assessed in the context of the Kyoto Protocol. Several studies suggest that the terrestrial biosphere is gaining carbon, but these estimates are obtained primarily by indirect methods, and the factors that control terrestrial carbon exchange, its magnitude and primary locations, are under debate. Here we present data of net ecosystem carbon exchange, collected between 1996 and 1998 from 15 European forests, which confirm that many European forest ecosystems act as carbon sinks. The annual carbon balances range from an uptake of 6.6 tonnes of carbon per hectare per year to a release of nearly 1 t C ha(-1) yr(-1), with a large variability between forests. The data show a significant increase of carbon uptake with decreasing latitude, whereas the gross primary production seems to be largely independent of latitude. Our observations indicate that, in general, ecosystem respiration determines net ecosystem carbon exchange. Also, for an accurate assessment of the carbon balance in a particular forest ecosystem, remote sensing of the normalized difference vegetation index or estimates based on forest inventories may not be sufficient.

Atmosphere↗
PubMed2000

An analogy between colour and spatial coding.

The early stages of colour coding are well established in that the trichromatic receptor stage is followed by a set of opponent colour channels. One interpretation of the sequence is that opponent channels carry unrelated aspects of the colour stimulus, unlike the cone channels. The overlap of the cone channels can be removed by decorrelating their spectral-sensitivity functions, and this procedure has been found to give opponent colour channels which match those found psychophysically. Since the known spatial-frequency channels also show considerable overlap, the question arises which aspects of the spatial stimulus are captured by decorrelating the spatial-frequency channels. The results of decorrelating the spatial-frequency channels are that the first decorrelated spatial filter acts as a broad bandpass filter which has a peak sensitivity at 7.9 cycles deg-1, and that the second decorrelated spatial filter acts as an opponent spatial-frequency channel, with a minimum output at a low (4.1 cycles deg-1) spatial frequency and a maximum output at a high (15.1 cycles deg-1) spatial frequency. The characteristics of the first decorrelated filter closely resemble the properties of the foveal perceptive field which have been used to explain the Hermann grid illusion. Thus, the decorrelation analysis produces a model for the functional organisation of the channel implementation at the neural and psychophysical levels, but which directly relates to the subjective appearance of the visual stimuli.

Color Perception↗
PubMed1999

Cerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine after intrathecal and epidural administrations in rabbits using microdialysis.

The aim of this work was to study the cerebrospinal fluid (CSF) bioavailability and pharmacokinetics of bupivacaine (BUP) and lidocaine (LID) administered separately in rabbits using microdialysis with retrodialysis calibration. Microdialysis probe and catheters were inserted under control of the view in the intrathecal or epidural spaces. The epidural disposition of BUP and LID after epidural administration of low (0.69 microM) and high (6.9 microM) doses was studied. Then, the intrathecal and plasma dispositions after separate intrathecal (0.2 microM) and epidural administration (6.9 microM) were investigated. The CSF binding of BUP and LID was linear in a range from 50 to 500 micrograms/ml, and the mean unbound CSF fraction at a concentration of 100 micrograms/ml was 39. 3 +/- 2.3% for BUP and 75.8 +/- 7.7% for LID. Epidural and intrathecal disposition of BUP and LID showed a biexponential decline. After epidural administration, the CSF concentrations of BUP and LID were much higher than those in plasma. After intrathecal administration, the plasma concentrations were below the limit of quantitation. Although the absorption rate of BUP appeared higher than that of LID, the mean CSF bioavailability of epidural BUP and LID was 5.5 and 17.7%, respectively. The unexpectedly higher CSF bioavailability of LID, the less lipophilic drug, may result from the difference in the processes competing for drug epidural removal.

Anesthetics, Local↗
PubMed1998

Decreased synthesis of glycosphingolipids in cells lacking vimentin intermediate filaments.

We are studying defects in glycosphingolipid synthesis in cells lacking vimentin intermediate filaments (vimentin-). Sugars can be incorporated into glycolipids whose ceramide is synthesized either de novo (pathway 1) or from sphingoid bases salvaged from hydrolysis of sphingolipids (pathway 2) and into glycolipids recycling from the endosomal pathway through the Golgi (pathway 3). Vimentin- embryonic fibroblasts, obtained from vimentin-knockout mice, incorporate less sugar into glycolipids than vimentin+ fibroblasts. Using two inhibitors of ceramide synthesis, beta-chloroalanine and fumonisin B1, we found the major defect in synthesis to be in pathway 2 and not in de novo synthesis. We used two additional approaches to analyze the functions of pathways 2 and 3. First, we used exogenous glucosylthioceramide ([14C]C8-Glc-S-Cer), a synthetic, nonhydrolyzable glycosphingolipid, as a precursor for synthesis of larger glycolipids. Vimentin- SW13 cells and embryonic fibroblasts glycosylated [14C]C8-Glc-S-Cer less extensively than their vimentin+ counterparts. Second, we used chloroquine to inhibit the hydrolysis of sphingolipids in endosomes and lysosomes. Chloroquine markedly decreased the incorporation of sugars into glycolipids larger than glucosylceramide. The defect in glycolipid synthesis in vimentin- cells probably results from impaired intracellular transport of glycolipids and sphingoid bases between the endosomal/lysosomal pathway and the Golgi apparatus and endoplasmic reticulum. Intermediate filaments may accomplish this function by contributing to the organization of subcellular organelles and/or by binding proteins that participate in transport processes.

Animals↗
PubMed1995

[Chronic compartment syndrome].

Among causes of leg pains, a usual disability in athletes, chronic exertional compartment syndrome is far from being uncommon. To the opposite, descriptions concerning the others compartments such as the forearm or thigh are still scarce and poorly documented. A variety of techniques have been described for the measurement of intramuscular pressure. Intramuscular pressure measurement is a valuable and essential tool for diagnosing a compartment syndrome, but it is somewhat controversial when the deep posterior compartment is concerned. Conservative treatment is unsuccessful, whereas surgical decompression yield favorable results; two procedures are performed subcutaneous fasciotomy or open fasciotomy.

Chronic Disease↗
PubMed1994

Effects of haloperidol, quinelorane, and lithium on regional neurotensin/neuromedin N concentrations: further evidence for neurotensin/neuromedin N-dopamine interactions.

In order to further characterize the pharmacologic mechanisms that mediate the antipsychotic drug-induced increase in neurotensin (NT) in nucleus accumbens and striatum, the effects of three weeks treatment with psychotherapeutic levels of lithium alone or in conjunction with haloperidol were compared to the ability of haloperidol alone to alter NT and neuromedin N (NMN) regional brain concentrations in rats. A separate experiment examined the ability of a selective dopamine D2 receptor agonist, quinelorane, to alter NT/NMN regional concentrations after three weeks of treatment as compared to haloperidol, a D2 receptor antagonist. Haloperidol (1 mg/kg) increased both NT and NMN concentrations in several brain regions and these parallel peptide increases were highly correlated. Lithium chloride (0.4 mM) had no effect, either alone or with haloperidol, on NT/NMN concentrations. Quinelorane (1 mg/kg), however, effectively increased both NT and NMN concentrations in the caudate nucleus and nucleus accumbens, as did haloperidol (2 mg/kg). These data indicate that the induction of NT and NMN, whose adjacent sequences are contained in a pro-hormone product of a single gene, occurs in tandem and remains proportional, as well as demonstrating that putative D2 receptor agonists can produce effects on NT/NMN systems that are similar to D2 receptor antagonists.

Animals↗
PubMed1993

[Unusual complication of venous thrombosis of the upper limb: pulmonary hypertension].

Although less frequent than that of the lower limbs, venous thrombosis of the upper limbs may cause pulmonary embolism. This embolism is usually moderate and facilitated by the delay or absence of anticoagulant treatment. We report the case of a young man who had multiple and recurrent embolism consecutive to thrombosis of the axillary and subclavian veins and who rapidly developed pulmonary arterial hypertension on previously healthy lungs. There was no venous disease of the lower limb. After a more than 2 years' period, the pulmonary arterial hypertension is still moderate, but the patient remains under long-term antivitamin K therapy, this being the only available treatment capable of preventing a deterioration that would result in post-embolic cor pulmonale and ultimately require lung transplantation.

Adult↗
PubMed1990

[Doppler evaluation of blood flow of the lower limb].

UNLABELLED: Regional blood flow measurement in the limbs (BFLL) is of special interest in order to evaluate the consequences of hypertension. The purpose of this study is to assess the interest of the Doppler ultrasound method in the BFLL measurement among normotensive or borderline hypertensives young male adults. BFLL reproducibility was evaluated among 23 healthy subjects aged 21 +/- 2 y, height 177 +/- 8 cm, weight 75 +/- 13 kg at day one (D1) and three day later (D3). Measurements were made basically after 20 minutes lying at rest and after cold pressor test (CPT). BFLL estimation depends on common femoral artery diameter (FAD) echographic measurement at the thigh root and on velocity time interval (VTI) calculation with pulsed wave doppler using controlled incident angle and sample volume. The following parameters were measured: mean arterial pressure (MAP) using Dinamap, heart rate (HR), FAD, common femoral artery cross sectorial area (A), VTI and peripheral arteriolar resistances (PAR). Basic and CPT results at D1 and D3 were compared using paired "t" test. RESULTS: [table: see text] Comparisons between basic state and CPT demonstrate a significant decrease of VTI and BFLL, a significant increase of PAR. D remained unchanged. Doppler ultrasound method is easy to use. Systolic femoral volume measurement is relatively insensitive to small transducer positioning variations so that the method reproducibility is satisfactory.

Adult↗
PubMed1989

Early arterial modifications in young patients with borderline hypertension.

Pulse wave velocity, used as an indicator of arterial distensibility, was recorded in 123 young male subjects, 63 untreated patients with borderline hypertension and 60 control subjects. The measurement was made with a continuous Doppler unit coupled to an ECG. In both groups mean age was similar, but mean arterial pressure was increased in borderline hypertensive compared with control patients. In comparison with controls, borderline hypertensives showed an increased pulse wave velocity. A significant correlation was observed between mean arterial pressure and pulse wave velocity in both populations, but the two regression lines were significantly different (covariance analysis). This result suggests that pulse wave velocity modifications in borderline hypertensives are not solely due to the elevated pressure, but also reflect structural or functional changes in the arterial tree.

Adolescent↗
PubMed1989

Increased vasodilator response during stimulation of cardiopulmonary baroreceptors in borderline hypertensives.

1. The effects of passive leg elevation on the forearm circulation were compared in 14 borderline hypertensive and 16 normotensive men. 2. In the supine position, mean arterial pressure (MAP), heart rate (HR) and forearm blood flow (FBF) were significantly greater in borderline hypertensives. 3. With leg raising, MAP and HR did not change significantly from basal values. FBF increased by +0.6 +/- 0.2 (s.e.m.) mL/min/100 mL (P less than 0.02) in normotensives and by + 1.3 +/- 0.2 mL/min/100 mL (P less than 0.001) in hypertensives (P for difference between groups less than 0.05).

Adolescent↗
PubMed1989

[Increased vasodilation response to the stimulation of low pressure mechanoreceptors in borderline hypertension].

Passive lifting of the lower limbs (antitilt) is a simple manoeuvre which stimulates low-pressure mechanoreceptors. Patients with borderline hypertension have an alteration of the arterial baroreflex modulated by an increased inhibitory effect of cardiopulmonary mechanoreceptors on vasomotor centres. The repercussions of antitilt on mean arterial pressure (MAP), heart rate (HR) and blood flow rate in the forearm (FRFA) were studied in 30 male subjects aged 18 to 25 years: 14 with untreated borderline hypertension ("patients") and 16 controls. FRFA was measured with a plethysmograph by means of a mercury constraint gauge. MAP was recorded during exploration with a DINAMAP instrument. The parameters were measured in recumbent position, then within minutes of the antitilt manoeuvre. In recumbent position the differences between patients and controls were: MAP 94.7 +/- 6 vs 84.7 +/- 7 mmHg (p less than 0.001); HR 76 +/- 13 vs 63 +/- 9 beats/min (p less than 0.01); FRFA 4.6 +/- 1.5 vs 3.5 +/- 1.4 ml/min/100 ml (p less than 0.05). Following antitilt, MAP and HR remained unchanged in the two groups, but there was a significant increase of FRFA in both controls (+ 0.6 +/- 0.2 ml/min/100 ml; p less than 0.02) and patients (+ 1.3 +/- 0.2 ml/min/100 ml; p less than 0.001). This increase was significantly greater in patients than in controls (p less than 0.05). This study shows that antitilt produces an increase of blood flow rate in the forearm that is more pronounced in patients with borderline hypertension than in controls. The stability of MAP and HR is in favour of non-actuation of the high-pressure arterial baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization.

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium.

Adenosine Triphosphate↗
PubMed1988

Perioperative morbidity in diabetics requiring coronary artery bypass surgery.

We retrospectively evaluated the operative results in 384 patients with diabetes mellitus operated on for ischemic coronary artery disease over a six-year period compared with a random group of 396 patients selected from 2,069 nondiabetic patients who underwent operation during the same study period. In our analysis of 13 preoperative and 5 intraoperative variables, diabetics revealed a significantly increased incidence of hypertension (p less than 0.05) and a smaller proportion of men (p less than 0.05). All other variables were not significantly different. The incidence of perioperative myocardial infarction, renal failure, neurological sequelae, leg infections, or thromboembolic events was similar in diabetic and nondiabetic patients. Hospital stay, however, was significantly increased in the diabetic group (p less than 0.05). The diabetic patients requiring intraaortic balloon counterpulsation had a significantly higher incidence of all postoperative complications analyzed compared with diabetics without balloon support (p less than 0.01), whereas the nondiabetic subset requiring intraaortic balloon counterpulsation exhibited only a significantly higher incidence of renal failure (p less than 0.01) and neurological complications (p less than 0.05). These results indicate that diabetes per se does not significantly increase morbidity in coronary bypass surgery.

Coronary Artery Bypass↗
PubMed1988

Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction.

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.

Animals↗
PubMed1988

[Plasma viscosity and erythrocyte filterability in borderline hypertension].

Hemorheological constants (plasma viscosimetry and erythrocyte filtrability index) were studied in 153 male subjects aged 19 to 23. Borderline hypertension defined by clinical criteria was found in 61 of these patients. Whilst there was no notable modification in plasma viscosity, by contrast there was a significant link between erythrometry and systolic and diastolic blood pressure. Erythrocyte deformability was all the more marked as blood pressure rose. These results would contrast with findings in the literature in cases of definite hypertension. The borderline nature of hypertension and the youth of the population was such that it could be considered that barometric factors had not yet influenced erythrocyte filtrability. The following hypothesis is therefore attractive: initially the red cell adapts itself to any possible increase in peripheral resistance. As the years go by its deformability is lessened by adverse changes affecting its membrane cytoskeleton.

Age Factors↗